This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The APOE [unreadable]4 allele is a major genetic risk factor Alzheimer's Disease (AD). Furthermore, over 25% of the general population are [unreadable]4 carriers. To enhance early identification of AD, studies are assessing the impact of [unreadable]4 on memory in older nondemented carriers. The literature is inconsistent and few studies have examined the impact of APOE [unreadable]4 in older professionals performing complex "real-world" tasks, such as flying an airplane. Our recent structural MRI study of 45 aviators found that [unreadable]4 carriers had poorer memory performance when learning a word list (Rey AVLT). Interestingly, no [unreadable]4-related differences in hippocampal volume were observed. The fMRI study underway aims to shed light on the neural mechanisms associated with the poorer word list learning observed in [unreadable]4 carriers. We have adapted the Rey AVLT to a visually presented format for fMRI. We predict that [unreadable]4 carriers will show overall lower activation than non-carriers during memory encoding in MTL regions (specifically the hippocampus), prefrontal, parietal and anterior cingulate regions. We are also testing spatial navigational memory, as navigation is crucial in aviation. Here, we are presenting a survey and route virtual reality task developed by Shelton and Gabrieli (2002;2005). We will assess the extent to which [unreadable]4 carriers with advanced FAA proficiency ratings show preserved activation during navigational memory encoding (APOE x Expertise interaction). Forty actively flying, FAA medically certified aviators with a range of proficiency ratings are being recruited for the study.